PB1902: FIRST EUROPEAN REAL-WORLD EVIDENCE PROSPECTIVE REGISTRY OF TAGRAXOFUSP, A CD123-DIRECTED THERAPY, FOR THE TREATMENT OF FIRST-LINE ADULT PATIENTS WITH BLASTIC PLASMACYTOID DENDRITIC CELL NEOPLASM
Authors: Uwe Platzbecker, Emanuele Angelucci, Pau Montesinos, Roberto M. Lemoni, Alexandros Spyridonidis, Marcello Riggi, Michael Zuurman, Mohamad Mohty
Journal: HemaSphere (2023)

Topic: 4. Acute myeloid leukemia - Clinical Background: Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an aggressive hematologic malignancy associated with a dismal prognosis (median overall survival [OS] of 8–14 months). BPDCN derives from plasmacytoid dendritic cells that overexpress interleukin-3 (IL-3) receptor alpha (CD123). Tagraxofusp (TAG), a first-in-class CD123-directed therapy comprising human IL-3 fused to a truncated diphtheria toxin payload, is the only approved treatment for BPDCN. In Europe, TAG is indicated for the first line (1L) treatment of adult patients (pts) with BPDCN. Collecting real-world clinical data through registry studies enables assessment of clinical outcomes in pts commonly underrepresented in clinical trials and provides further information about a drug’s effectiveness and safety. Herein, we describe the first real-world evidence European prospective registry in 1L pts with BPDCN receiving TAG, which was designed to meet requirements outlined in the marketing authorization of the European Commission (January 7, 2021). Aims: To investigate the efficacy and safety of 1L TAG for pts with BPDCN in clinical practice. Methods: This is a noninterventional, single-arm, post-authorization study in pts aged ≥18 years who have a diagnosis of BPDCN and are to be treated (or recently started treatment) with TAG monotherapy as 1L treatment, per physician’s decision. Pts will be prescribed TAG under real-world routine clinical practice conditions (12 mcg/kg intravenously [IV] once daily on days 1–5 of a 21-day cycle, per the summary of product characteristics recommendation). A minimum of 80 pts at 40–55 sites in Europe will be included over approximately 4 years. The primary endpoints are rate of complete response (CR), defined as CR + clinical CR (CR with residual skin abnormality not indicative of active disease) after 3 months of treatment, and safety of TAG including the incidence and severity of capillary leak syndrome (CLS). Secondary endpoints include OS, progression-free survival, best overall response, duration of response, number of pts bridging to stem cell transplant, TAG dose interruptions or administration of IV albumin supplementation in pts with CLS or CLS symptoms, as well as the incidence and severity of adverse events of special interest (including CLS, and hepatic, renal, and cardiac events). Quarterly data collection is anticipated, as well as collection at screening, enrollment, early discontinuation, and study end (Figure). Data collection will start 4–6 months post-protocol approval. Recruitment period will be 48 months from the start of data collection. An interim report will be created every 24 months from start of data collection. The end of data collection for the final report will be finalized 18 months after last enrolled pt’s first visit, with a final report 8 months after end of data collection. Analyses will be performed using descriptive statistics. Survival data will be summarized using the Kaplan-Meier method. Subgroup analyses for effectiveness and safety may be performed, based on gender, age, or baseline Eastern Cooperative Oncology Group performance status. Enrollment is planned to start in Q1/2023, and the opening of new centers is ongoing in Austria, Germany, and Italy. Upon study finalization, a complementary comparative analysis of effectiveness and safety data from the TAG registry with a retrospective clinical cohort will be undertaken using appropriate methodology, such as propensity score matching or inverse probability treatment weighting.Results:Summary/Conclusion: Keywords: Targeted therapy, Myeloid malignancies